The phosphorylation of nonhistone chromosomal proteins (NHCP) appears to exert a regulatory influence on transcription in eukaryotic cells. The recent discovery that cordycepin (3'-deoxyadenosine) can inhibit normal and neoplastic nuclear protein kinase activities in vitro has prompted an investigation of the role of phosphorylation in the action of this and related drugs. The phosphorylation of NHCP in vitro in isolated nuclei will be used to study the effect that cordycepin has on various classes of NHCP as determined by isoelectric focusing. These studies will be extended to L1210 cells in vitro to correlate the effects of cordycepin on nuclear phosphorylation and RNA synthesis. The latter system will also allow a determination of the effect that the adenosine deaminase inhibitor, 2'-deoxycoformycin, has on the action mediated by cordycepin on the phosphorylation of NHCP.